Chinese Herb Has Applications as Immunosuppressant, Anti-Cancer Drug
Contents
Introduction
Triptolide as Immunosuppressant
Triptolide as Anti-Cancer Drug
Introduction (Back to Top)
A perennial herb used by the Chinese for hundreds of years to relieve rheumatoid arthritis symptoms has much more far-reaching medicinal qualities, according to two studies conducted at the Stanford University School of Medicine. Scientists found that the active component of the herb is a drug that can suppress an overactive immune system, prevent inflammation, and kill cancer cells. The results of the study were published in the May 7 issue of the Journal of Biological Chemistry.
People have known for 20 years that preparations from Tripterygium Wilfordii hook, a vine that grows in Southern China, have medicinal properties, but the way that the herb worked inside the body was not previously known. Using a pure preparation of triptolide, the active compound within the plant, the Stanford scientists found that the drug exerts its effects by preventing activation of a DNA-binding protein, NF-KB, after it has partnered with its DNA target. This protein is a pivotal molecule that, once active, escalates an immune response by switching on other immunologically important genes. Figuring out exactly how the drug works on a molecular scale has assisted the two research teams in their efforts to determine the cause of the biological effects valued by Tripterygium users.
Triptolide as Immunosuppressant (Back to Top)
Peter Kao, assistant professor of pulmonary and critical care medicine at Stanford, led a group that studied interactions between triptolide and other immunologically significant molecules and genes. Kao and his colleagues have found that the way triptolide tempers the immune system is completely different than the way traditional immunosuppressants, such as cyclosporin A and FK506, work.
Theoretically, these immunosuppressants can also be given to people suffering from autoimmune or inflammatory diseases where the immune system has gone awry. In practice, however, the severe adverse side effects of these drugs prevent their use in patients whose conditions are not life threatening. Because triptolide works in a different way, it may prove to be a useful alternative.
"Our work shows that [triptolide] is more potent than more traditional immunosuppressants such as cyclosporin and FK506,'' said Kao. He sees promise in using triptolide to temper the immune system and treat patients suffering from graft vs. host disease, inflammatory diseases like rheumatoid arthritis, and autoimmune diseases like multiple sclerosis.
Stanford scientists who collaborated on Kao's study include Daoming Qiu, Guohua Zhao, Yosuke Aoki, and Lingfang Shi. Medical school graduate students on the project were Anne Uyei, Saman Nazarian, and James Ng. Funding for the study was provided by grants from the National Institutes of Health and gifts from Pharmagenesis Inc. (Palo Alto, CA) and the Donald E. and Delia B. Baxter Foundation.
Triptolide as Anti-Cancer Drug (Back to Top)
Glenn Rosen, also an assistant professor in the department of pulmonary and critical care medicine, led a group that focused on the tumor-killing properties of triptolide. Rosen was primarily searching for agents that would augment killing of tumor cells by a class of compounds related to tumor necrosis factor (TNF). He found that triptolide cooperates with TNF to cause cancerous cells to die, but also discovered that triptolide is capable of killing tumor cells on its own.
Triptolide and TNF-like compounds kill tumor cells by forcing apoptosis, a kind of cellular suicide. However, TNF and related molecules are themselves toxic to cells and can cause bad side effects in patients. Because triptolide does not activate the NF-KB molecule, these side effects are expected to be greatly reduced in cancer patients treated with the herbal drug, said Rosen.
Rosen's optimism about the drug is bolstered by the fact that triptolide, like the popular anti-cancer drug taxol (which comes from the bark of the Pacific Yew tree), kills cancer cells independent of the p53 gene. Chemotherapy to treat solid tumors is often hindered because cancer cells frequently become resistant to the drugs being used. A common cause of this drug resistance is changes to the p53 tumor suppressor gene. By causing tumor cells to die in a p53-independent way, drugs like taxol and triptolide are able to kill cells from cancers that are found to be resistant to other chemotherapy agents.
Stanford scientists who collaborated on Rosen's study include Kao, Wen-teh Chang, Kye Young Lee, and Daoming Qiu. The study was supported by a California Breast Cancer Research Grant and gifts from Pharmagenesis and Jan DiCarli.
The pure preparations of triptolide used in both studies were provided by Pharmagenesis Inc.
For more information: Peter Kao, Assistant Professor, Pulmonary and Critical Care Medicine, Stanford University School of Medicine, 300 Pasteur Dr. #M121 Stanford CA 94305-5119. Tel: 650-725-0570. Fax: (650) 725-5489. Email: peterkao@leland.stanford.edu. Or contact: Glenn Rosen, Assistant Professor, Pulmonary and Critical Care Medicine, Stanford University School of Medicine. Tel: 650-725-9536. Fax: (650) 725-5489. Email: grosen@leland.stanford.edu.